NF-κB memory coordinates transcriptional responses to dynamic inflammatory stimuli

Area of Science:

• Cellular Biology
• Systems Biology
• Immunology

Background:

• Cellular communication involves interpreting multiple dynamic signals.
• The impact of prior inflammatory stimuli on subsequent transcriptional responses remains unclear.

Purpose of the Study:

• To systematically profile the NF-κB response to different signal sequences in single cells.
• To understand how cells store and process information from sequential inflammatory stimuli.

Main Methods:

• High-throughput microfluidic live-cell analysis.
• Information theory to quantify signal encoding.
• Small-molecule inhibition, computational modeling, and gene expression profiling.

Main Results:

• NF-κB dynamics store short-term signal history, influencing subsequent responses.
• Prior pathogenic or cytokine signals modulate the NF-κB response to new stimuli.
• Stimulus-dependent negative feedback modules drive information encoding in NF-κB signaling.

Conclusions:

• Signal transduction networks can process sequences of inflammatory stimuli.
• NF-κB signaling exhibits memory, encoding information about prior stimuli.
• This mechanism aids in coordinating cellular responses in complex dynamic environments.